ExPath Students and their Research

Applying patient whole-exome and whole-genome sequencing data in conjunction with the development of a novel integrative genomics pipeline to investigate genetic etiologies underpinning a variety of idiopathic congenital neurological conditions including Chiari malformation, congenital hydrocephalus, and arachnoid cysts.Mentor: Kristopher Kahle

Investigating the Barriers to Reprogramming in Pig Induced Pluripotent Stem Cells: Cardiovascular tissue engineering is a rapidly advancing field that is producing new stem cell-based therapeutics for heart disease, but is being held back by the lack of a robust cardiovascular model that recapitulates the human system for safety and efficacy tests. We are attempting to provide this model in the pig by producing truly pluripotent pig induced pluripotent stem cells to be used as a platform to test allogeneic stem cell-based transplantation.Mentor: Yibing Qyang

Exploring mechanistic questions about complex liver diseases using genetic screens.Mentor: Silvia Vilarinho

Exploring alterations in tumor suppressor genes that promote tumor growth in EGFR-driven lung adenocarcinomas and elucidating potential therapeutically targetable pro-tumorigenic pathways.Mentor: Katerina Politi

Identifying synthetic lethal drug interactions in brain cancer for the development of novel therapeutics.Mentor: Ranjit Bindra

"Investigating the potential leukemogenic role of the RNA-binding motif protein 15 (RBM15) when it is aberrantly fused with the megakaryoblastic leukemia 1 (MKL1) protein through in vitro and in vivo models of acute megakaryoblastic leukemia (AMKL) – thereby contributing to defining novel strategies in regulating hematopoiesis and treating leukemia.”Mentor: Diane Krause

Studying mechanisms of acquired resistance to KRAS-targeting therapies based on pharmacologic and genetic vulnerabilities using drug and CRISPR screens in KRAS knockout pancreatic cancer cells and dissecting KRAS signaling network via optogenetic tools.Mentor: Mandar Muzumdar

Aging-associated changes (mRNA, protein and epigenetic DNA methylation) in liver hepatocyte populations during homeostatic and damage conditions.Mentors: Albert Higgins-Chen

Characterizing resistance mechanisms for antibody-drug conjugates (ADCs) and designing diagnostic assays for ADC treatments: ADCs are a novel class of cancer therapy that links antibody specificity to potent cytotoxic molecules. Although showed significant improvement in clinical trials, ADCs still exhibit resistance and toxicities. Hence, I aim to investigate the resistance mechanisms for ADCs, identify predictive biomarkers for ADC responders, and design standardized and clinically applicable diagnostic assays for screening.Mentor: David Rimm

The relationship between the gene TSP2 and diseases, and TSP2-related biomaterials.Mentor: Themis Kyriakides

"Towards overcoming therapeutic resistance in brain metastatic NSCLC: Central nervous system (CNS) metastasis is frequently observed in EGFR-mutant non-small cell lung cancer (NSCLC) accompanied by the development of lesions resistant to Osimertinib. We are focusing on the contributions of the tumor microenvironment and extracellular matrix to the persistence of metastatic-resistant NSCLC clones."Mentor: Don Nguyen

Characterization of cerebrospinal fluid factors influencing leptomeningeal metastases.Mentor: Don Nguyen

Leveraging epigenetic targets to elucidate mechanisms of brain metastasis: Caro is interested in identifying novel mechanisms via which epigenetic regulators control the metastasis of lung adenocarcinomas.Mentor: Don Nguyen

PD-L1 expression on multiple immune cell types as predictive biomarker to anti-PD-1 blockade therapy: To establish a predictive model to assess the potential for clinical response to anti-PD-1 therapy.Mentor: Ranjit S. Bindra

AMKL is a rare leukemia characterized by the improper development of megakaryocytes. In neonates, AMKL is most often caused by a genetic translocation resulting in the RBM15-MKL1 fusion protein. Madeline's work focuses on the effect of this fusion protein on normal and malignant hematopoiesis with the goal of elucidating the mechanism by which it promotes leukemogenesis.Mentor: Diane Krause

Mentor: Qin Yan

Investigating pathology of aging, both to better understand and capture hallmarks of the aging process using epigenetics and also to better inform therapeutic rationales to extend health-span.Mentor: Themis Kyriakides

Understanding the epigenetic and pathogenic mechanisms of PPM1D positive tumors associated with Diffuse Intrinsic Pontine Glioma (DIPG), a rare pediatric cancer, in the hopes of developing viable therapeutic treatments.Mentor: Ranjit S. Bindra

Investigating the epigenetic mechanisms of reprogramming and aging in fibroblasts.Mentor: Albert Higgins-Chen

Investigating the mechanism of novel radiosensitizers for glioblastoma therapy.Mentor: Ranjit S. Bindra

Next-generation diagnostic approaches for HER2-low breast cancer and trastuzumab deruxtecan therapy: The current immunohistochemical (IHC) assays for determining HER2-low status are no better than a coinflip (due to an estimated 75% discordance rate amongst pathologists scoring 0 vs. 1+/2+). These legacy assays for HER2 were designed over 20 years ago to detect amplified HER2 cases, and are now are being wrongly applied to select patients for emerging HER2-low therapies (e.g. trastuzumab deruxtecan). In the Rimm lab, we have developed a solution: a high-sensitivity HER2 assay that is designed to quantify unamplified, low HER2 expression rather than rely on subjective semi-quantitative scoring by pathologists using legacy IHC assays. We plan to carefully evaluate the HS-HER2 assay and it's predictive value towards T-DXd response to in comparison to the legacy IHC assays. We expect that our results will encourage adoption of high-sensitivity, analytic assays for HER2 expression that oncologists can use to be certain their patients are receiving the best treatment option available. My research will also include investigating the biology of HER2-low breast cancer and the molecular mechanisms outside of HER2 expression associated with T-DXd antibody-drug conjugate response. Mentor: David Rimm

Aging is associated with chronic inflammation that contributes to the development and progression of age-related pathologies. Mitochondrial DNA (mtDNA) has recently been identified as a pathogenic signal that is able to activate several pro-inflammatory signaling pathways. My work involves investigating the contribution of mtDNA signaling to the aging process and understanding how this signaling is regulated. Mentor Gerald Shadel, PhD

Exploring mechanisms of therapy resistance in EGFR-driven non-small cell lung cancer (NSCLC): This project aims to characterize off-target mechanisms that contribute to therapy resistance and identify exploitable vulnerabilities to resensitize NSCLC tumors to therapy.Mentor: Katerina Politi

Genetic and Metabolic Mapping of Obesity-induced Hepatocellular Carcinoma: I hope to map changes in molecular networks and metabolic programs from the progression of non-alcoholic fatty liver disease (NAFLD) to HCC. Through metabolic and genomic tracing, we can isolate molecular leads to evaluate significance in HCC development and identify therapeutic targets.Mentor: Carlos Fernandez-Hernando

Investigations in telomere maintenance and regulation by Pot1b. To explore the role of Pot1b in telomere length maintenance during telomerase-mediated telomere elongation and alternative lengthening of telomeres.Mentor: Sandy Chang

Melanoma immunobiologyMentor: Marcus Bosenberg

My project involves the investigation of the role of extracellular vesicles in inflammation, tissue remodeling and repair. Via genetic and synthetic biology approaches, I aim to decipher the role they play in these processes and exploit them for the development of novel constructs consisting of hydrogels, extracellular vesicles, and drugs. Such constructs will be employed in regenerative medicine applications and the treatment of chronic wounds.Mentor: Themis Kyriakides

Cellular Response to Mitochondrial DNA Stress in Cellular Aging.Mentor: Keith Choate

Researching the role of RNA splicing in pancreatic cancer with the goal of identifying novel therapeutic targets that can improve both the quality of life and survival of patients.Mentor: Luisa Escobar-Hoyes